Mechanisms of Morphogenesis; Systems Biology of Development; Animal Models of Birth Defects; Biological Functions of Proteoglycans; Mechanisms of Carcinogenesis; Dynamics of Stem Cell Systems; Genetic Origins of Complex Traits
Grass Traveling Speaker, Society for Neuroscience 1995
David and Lucile Packard Fellowship for Science and Engineering 1988
Javits Neuroscience Investigator Award (NIH) 1998
Elected, American Society for Clinical Investigation 2000
"Excellence in Teaching" Award, Division of Undergraduate Education, UC Irvine 2001
Marlene A. DeLuca Lecturer, UC San Diego, Department of Chemistry and Biochemistry 2008
Elected, Fellow of the American Association for the Advancement of Science (AAAS) 2008
The Lander lab is interested in the molecular mechanisms by which cells communicate. We focus on two kinds of pathways--those involving growth factors and their receptors, and those involving molecules of the extracellular matrix and their receptors. We study these pathways in the context of both mammalian (mouse) development and cancer biology, since growth control and cell-matrix interactions are critical to both processes. We also focus on cells of the nervous system, to understand why the growth that occurs during developing often fails to recur after injury (e.g. spinal cord injury).
We are able to work in such a wide range of areas by (1) emphasizing fundamental aspects of cellular communication that have broad applications, and (2) utilizing approaches such as transgenic and "knockout" mice, that enable the roles and effects of molecules to be studied in the context of an entire organism.
One group of projects in the lab concerns "co-receptors", cell-surface molecules that regulate the interaction between soluble growth factors and their cell-surface receptors. We have identified a novel co-receptor for BMPs (bone morphogenetic proteins) and are studying the roles of Heparan Sulfate Proteoglycans (HSPGs) as co-receptors for a variety of growth factors, including those that drive tumor development and pattern the developing nervous system. We have used "knockout" technology to generate mice that are mutant for particular HSPGs, and are also working with mice that are mutant for some of the biosynthetic enzymes required to make HSPGs. We are also using modeling approaches to understand how HSPGs influences the kinetic parameters of growth factor-receptor interaction.
Another area of investigation is the role of Chondroitin Sulfate Proteoglycans as scaffolding molecules that immobilize secreted signaling molecules. We study these in the developing brain, where they appear to play a role in localizing the molecules that \ guide growing axons.
Another topic concerns a phenomenon called integrin activation, in which cells regulate the efficacy of their integrins, the major cells surface receptors for the extracellular matrix. We have obtained evidence that a decline in integrin activation accounts for some of the inability of mature central nervous system neurons to re-grow their axons after injury. We are using viral vectors to introduce genes into neurons of adult animals, in an attempt to reverse this decline.
"Affinity Co-Electrophoresis" U.S. Patent No. 5,116,483, issued May 26, 1992.
"Viral Inactivation Method and Apparatus" with T.P. Castor. U.S. Patent application filed March 1992.
"Glypicans for the Detection and Treatment of Human Carcinoma" with M. Korc. U.S. Patent application filed October 1999.
Muto, A., A.L.Calof, A.D. Lander and T.F. Schilling (2011) Multifactorial origins of heart and gut defects in nipbl-deficient zebrafish, a model of Cornelia de Lange Syndrome. PLoS Biology, 9, e1001181. PMCID: PMC3201921
Nahmad, M and A.D. Lander (2011) Spatiotemporal mechanisms of morphogen gradient interpretation. Curr. Opin. Genet. Devel. 21, 726-31.
Gokoffski, K.K., H.-H. Wu, C.L. Beites, J. Kim, E.J. Kim, M.M. Matzuk, J.E. Johnson, A.D. Lander and A.L. Calof (2011) Activin And GDF11 collaborate in feedback control of neuroepithelial stem cell proliferation and fate. Development, 138, 4131-4142. doi:10.1242/dev.065870.
Lei, J., F.Y.M. Wan, A.D. Lander and Q. Nie (2011) Robustness of signaling gradient in Drosophila wing imaginal disc. Discrete & Continuous Dynamical Systems Series B, 16(3), 835 - 866. doi:10.3934/dcdsb.2011.16.835
Lander, A.D., Q. Nie, B. Vargas and F.Y.M. Wan (2011) Size-normalized robustness of Dpp gradient in Drosophila wing imaginal disc. J. Mechanics of Materials and Structures, 6, 321-350.
Lander, A.D. (2011) The individuality of stem cells. BMC Biol, 9, 40. doi:10.1186/1741-7007-9-40.
Lander, A.D. (2011) Pattern, growth and control. Cell 144, 955-969. PMID: 21414486
Chou, C.S., W.-C. Lo, K. K. Gokoffski, Y.-T. Zhang, F.Y.M. Wan, A. D. Lander, A. L. Calof, and Q. Nie (2010) Spatial dynamics of multi-stage cell lineages in tissue stratification. Biophys. J., 99, 3145-3154. PMCID: PMC2980753
Kuo, W.-J., M. Digman and A.D. Lander (2010) Heparan sulfate acts as a BMP co-receptor by facilitating ligand-induced receptor hetero-oligomerization. Mol. Biol. Cell 21, 4028-4041. doi 10.1091/mbc.E10-04-0348. PMCID: PMC2982130
Potkin, S. G., F. Macciardi, M. Vawter, G. Guffanti, Q. Wang, J.A. Turner, A. Lakatos, M.F. Miles, A. Lander, and X. Xie (2010) Identifying Gene Regulatory Networks in Schizophrenia. Neuroimage 53, 839-847. PMCID: PMC3055795
Lander, A.D. (2010) The edges of understanding. BMC Biol. 8: 40doi:10.1186/1741-7007-8-40. PMCID: PMC2864098
Gokoffski, K.K., Kawauchi, S., H.-H. Wu, R. Santos, P.W.L. Hollenbeck, A.D. Lander and A.L. Calof (2009) Feedback regulation of neurogenesis in the mammalian olfactory epithelium: New insights from genetics and systems biology. In: Neurobiology of Olfaction, A. Menini, Ed. CRC press. ISBN: 9781420071979
Lander, A.D. (2009) The “stem cell” concept: is it holding us back? J. Biol. 8, 70. doi:10.1186/jbiol177
Kawauchi, S., R. Santos, M.E. Lopez-Burks, C.M. Young, M.P. Hoang, A. Chua, T. Lao, M.S. Lechner, L. Kitzes, B. Hallgrimsson, A.L. Calof and A.D. Lander (2009) Multiple organ system defects and transcriptional dysregulation in a mouse model of Cornelia de Lange Syndrome. PLoS Genetics, 5: e1000650. doi:10.1371/journal.pgen.1000650
Liu, J., M.B. Dillencourt, L.F. Bic, D. Gillen and A.D. Lander (2009) Distributed Individual-Based Simulation. In: Euro-Par 2009—Parallel Processing: Proceedings of the 15th International European Conference on Parallel and Distributed Computing, Lecture Notes in Computer Science, vol. 5704. H. Sips, D. Epema and H-X. Lin, Eds. Springer, Heidelberg. pp590-601. doi:10.1007/978-3-642-03869-3_56
Jen, Y-H, M. Musacchio and A.D. Lander (2009) Glypican-1 controls brain size through regulation of FGF signaling in early neurogenesis. Neural Development, 4:33, doi:10.1186/1749-8104-4-33. PMCID: PMC2746204
Lander, A.D., W.-C. Lo, Q. Nie and F.Y.M. Wan (2009) The measure of success: constraints, objectives and tradeoffs in morphogen-mediated patterning. Cold Spring Harbor Perspectives in Biology 1, a002022: doi: 10.1101/cshperspect.a002022. PMCID: PMC2742077
Lander, A.D., Q. Nie, F.Y.M. Wan, and Y.-T. Zhang (2009) Localized Ectopic Expression of Dpp Receptors in a Drosophila Embryo. Studies in Applied Mathematics, 123, doi: 10.1111/j.1467-9590.2009.00450.x.
Beites, C.L., P.L.W. Hollenbeck, J. Kim1, R. Lovell-Badge, A.D. Lander and A.L. Calof 1 (2009) Follistatin modulates a BMP autoregulatory loop to control size and patterning of sensory domains in developing tongue. Development,136 (13):2187-2197. PMCID: PMC2729339
Kawauchi, S., J. Kim, R. Santos, H.-H. Wu, A.D. Lander and A.L. Calof (2009) Foxg1 promotes olfactory neurogenesis by antagonizing Gdf11. Development 136, 1453-1464. PMCID: PMC2674256
Lander, A.D., K. K. Gokoffski, Frederic Y. M. Wan, Qing Nie and Anne L. Calof (2009) Cell Lineages and the Logic of Proliferative Control. PLoS Biology 7, e15:doi:10.1371/journal.pbio.1000015. PMCID: PMC2628408
Lo, W.-C., C.S. Chou, K.K. Gokoffski, F.Y.M. Wan, A.D. Lander, A.L. Calof and Q. Nie (2009) Feedback regulation in multistage cell lineages. Math Biosci Eng., 6, 59-82.
Whipple C.A., A.D. Lander and M. Korc (2008) Discovery of a novel molecule that regulates tumor growth and metastasis. ScientificWorldJournal 8,1250-1253.
Aikawa, T, C. Whipple, M.E. Lopez, J. Gunn, A. Young, A.D. Lander and M. Korc (2007) Glypican-1 modulates the angiogenic and metastatic potential of human and mouse cancer cells. J Clin. Invest. 118, 89-99.
White, R.J., Q. Nie, A.D. Lander and T.F. Schilling (2007) Complex regulation of cyp26a1 creates a robust retinoic acid gradient in the zebrafish embryo. PLoS Biology, 5, e304. PMCID: PMC2080651
White, R.J., Q. Nie, A.D. Lander and T.F. Schilling (2007) Shaping the retinoic acid morphogen gradient in the zebrafish embryo by regulation of degradation. PloS Biology, 5, e304.
Zhang, Y.T., A.D. Lander and Q. Nie (2007) Computational analysis of BMP gradients in dorsal-vental patterning of the zebrafish embryo. J. Theor. Biol., 248, 579-589.
Lander, A.D. (2007) Morpheus Unbound: Re-imagining the Morphogen Gradient. Cell, 128, 245-256.
Lander, A.D., Q. Nie and F.Y.M. Wan (2006) Membrane associated non-receptors and morphogen gradients. Bulletin of Math Biology. 69, 33-54.
Lander, A.D., Q. Nie and F.Y.M. Wan (2006) Internalization and End Flux in Morphogen Gradient Formation. J. Computat. Appl. Math. 190, 232-251.
Ding, K., J. A., Sánchez-Duran, M. Korc, and A.D. Lander (2004) Growth factor-induced shedding of syndecan-1 confers glypican-1 dependence on mitogenic responses of cancer cells. J. Cell Biol., submitted.
Murray, R.C., D. Navi, J. Fesenko, A.D. Lander, and A.L. Calof (2003) Widespread defects in the primary olfactory pathway caused by loss of MASH1 function. J. Neurosci. 23, 1769-1780
Tsai, E.S., S. J. Haraldson, J. Baratta, A.D. Lander, J. Yu and R. T. Robertson (2002) Basal forebrain cholinergic cell attachment and neurite outgrowth on organotypic slice cultures of hippocampal formation, Neuroscience 115, 815-827.
Lander, A.D., Q. Nie and F.Y.-M. Wan (2002) Do morphogen gradients arise by diffusion? Developmental Cell 2, 785-796.
Matsuda, K., H. Maruyama, F. Guo, J. Kleeff, J. Itakura, Y. Matsumoto, A.D. Lander and M. Korc (2001) Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells. Cancer Research, 61, 5562-5569.
Karumanchi S.A., V. Jha , R. Ramchandran , A. Karihaloo , L. Tsiokas , B. Chan, M. Dhanabal, J.-i. Hanai, G. Venkataraman, Z. Shriver, N. Keiser, R. Kalluri, H. Zeng, D. Mukhopadhyay, R.L. Chen, A.D. Lander, K. Hagihara, Y. Yamaguchi, R. Sasisekharan, L. Cantley, and V. P. Sukhatme (2001) Cell Surface Glypicans Are Low-Affinity Endostatin Receptors. Molecular Cell 7, 811-822.
Chen, R.L. and A.D. Lander (2001) Mechanisms underlying preferential assembly of heparan sulfate on glypican-1. J. Biol. Chem. 276, 7507-7517.
Zhu, Z.-w., H. Friess, L. Wang, M. Abou-Shady, A. Zimmermann, A.D. Lander, M. Korc, J. Kleeff and M. Büchler (2001) Enhanced glypican-3 expression differentiates the majority of hepatocellular carcinomas from benign hepatic disorders. Gut 48, 558-64.
Chien, R., W. Zeng, S. Kawauchi, M.A. Bender, R. Santos, H.C. Gregson, J.A. Schmiesing, D. Newkirk, X. Kong, A.R. Ball Jr., A.L. Calof, A.D. Lander, M Groudine and K. Yokomori (2011) Cohesin mediates chromatin interactions that regulate mammalian ?-globin expression. J. Biol. Chem., 286, 17870-17878. doi/10.1074/jbc.M110.207365. PMCID: PMC3093862
Emerling D.E., and A.D. Lander (2000) Using organotypic tissue slices as substrata for the culture of dissociated cells. Methods Mol Biol 139, 245-256.
Ivins J.K., P.D. Yurchenco, and A.D. Lander (2000) Regulation of neurite outgrowth by integrin activation. J. Neurosci. 20, 6551–6560.
Lander, A.D. and S. Selleck (2000) The elusive functions of proteoglycans: In vivo veritas. J. Cell Biol. 148, 227-232.
Kleef, J, T. Ishiwata, A. Kumbasar, H. Friess, M.W. Büchler, A.D. Lander and M. Korc (1998) The cell surface heparan sulfate proteoglycan glypican-1 is an essential regulator of growth factor action in pancreatic carcinoma cells, and is overexpressed in human pancreatic cancer. J. Clin. Invest. 102, 1662-1673.
Lander, A.D. (1998) Proteoglycans: Master regulators of molecular encounter? Matrix Biology 17, 465-472.
Emerling, D.E. and A.D. Lander (1996) Inhibitors and promoters of thalamic neuron adhesion and outgrowth in embryonic neocortex: functional association with chondroitin sulfate. Neuron, 17, 1089-1100.
Analysis of Proteoglycans Involved in Brain Development
Co-Receptor Mechanisms in BMP Signaling
Morphogen Systems: A Joint Math and Experimental Initiative
Role of Glypicans in Pancreatic Cancer
Human Frontiers Science Program:
Heparan sulfate proteoglycans in morphogen gradient formation
P50 - Systems Biology of Morphogenesis and Spatial Information Flow
HHMI - Howard Hughes Medical Institute through the HHMI-NIBIB Interfaces initiative - Mathematical, Computational, and Systems Biology
NIH (NIGMS) A National Short Course in Systems Biology: Tackling Spatial Dynamics in Cells and Tissues
NIH (NIBI) Mathematical, Computational and Systems Biology
NIH (NICHD) Training Program in Systems Biology of Development
NIH (NICHD) Role of Cohesin in Developmental Gene Regulation
NIH (NCI) Feedback, lineages and cancer: A multidisciplinary approach
This GO (“Grand Opportunities”)
NIH (NINDS) The morphogen and selector gene network in the dorsal telencephalic midline
Templeton Foundation From Complex Systems to Complex Traits
NIH (NIGMS) Principles of Robust Developmental Patterning
NIH (NICHD) Vertebrate Animal Models of Cornelia de Lange Syndrome
NIH (NIGMS) Systems Biology of Morphogenesis and Spatial Information Flow
American Society for Cell Biology
Society for Neuroscience
Society for Developmental Biology
American Society for Clinical Investigation
American Society for Matrix Biology
Clinical Advisory Board
Cornelia de Lange Syndrome Foundation 2002
Developmental Biology and Genetics
Mathematical and Computational Biology
Developmental Biology Center
Cancer Research Institute
Center for Complex Biological Systems